2-nitroveratryl as a photocleavable thiol-protecting group for directed disulfide bond formation in the chemical synthesis of insulin

JA Karas; DB Scanlon; BE Forbes; I Vetter; RJ Lewis; J Gardiner; F Separovic; JD Wade; MA Hossain

Journal article

2-nitroveratryl as a photocleavable thiol-protecting group for directed disulfide bond formation in the chemical synthesis of insulin

JA Karas, DB Scanlon, BE Forbes, I Vetter, RJ Lewis, J Gardiner, F Separovic, JD Wade, MA Hossain

Chemistry (Weinheim an der Bergstrasse, Germany) | Published : 2014

DOI: 10.1002/chem.201403574

Abstract

© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Chemical synthesis of peptides can allow the option of sequential formation of multiple cysteines through exploitation of judiciously chosen regioselective thiol-protecting groups. We report the use of 2-nitroveratryl (oNv) as a new orthogonal group that can be cleaved by photolysis under ambient conditions. In combination with complementary S-pyridinesulfenyl activation, disulfide bonds are formed rapidly in situ. The preparation of Fmoc-Cys(oNv)-OH is described together with its use for the solid-phase synthesis of complex cystine-rich peptides, such as insulin.

University of Melbourne Researchers

John Karas Author

Frances Separovic Author

Akhter Hossain Author

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Grants

Funding Acknowledgements

This research was partially funded by the NHMRC Project grants 1023321 and 1023078 to M. A. H. and J.D.W. and C.S.I.R.O. (Australia). We thank the following people: Feng Lin for amino acid analysis, Dr. Keiko Hojo for assistance with the racemization study, Dr. Julien Tailhades for his expertise in iso-acyl dipeptides, Assoc. Prof. Uta Wille and Dr. Catrin Goeschen for access to their photoreactor, and Assoc. Prof. Craig Hutton and Dr. Jade Cottam for access to their polarimeter. J.D.W. is an NHMRC (Australia) Principal Research Fellow. Research at the Florey Institute of Neuroscience and Mental Health is supported by the Victorian Government Operational Infrastructure Support Program.